Utilization of colorectal cancer screening tests: a systematic review and time trend analysis of nationally representative data

Summary Background The substantial and increasing global burden of colorectal cancer (CRC) underscores the imperative to enhance implementation and utilization of effective CRC screening offers. Therefore, we examined the lifetime and up-to-date use of CRC screening tests across various countries, and described utilization trends over time. Methods We conducted a systematic review on the extent and recent trends of utilization of CRC screening tests among people 45 years or older in different countries around the globe. PubMed/Medline, Web of Science, and Embase electronic databases were screened for eligible studies from inception to June 30, 2024. The study protocol was registered with international prospective register of systematic reviews (PROSPERO) (CRD42023391344). Findings A total of 50 studies, based on nationally-representative data, were finally included - 27 from the United States (US) and 23 from other countries. The overall utilization of CRC screening has steadily increased over time in many countries, reaching 74.9% in Denmark in 2018–2020, 64% in Korea in 2020, and 72% in the US in 2021. Nevertheless, the utilization rates remain far below the national or continental targets in most countries. In contrast to European and Asian countries, where screening was predominantly fecal test-based, the approach in the US was primarily driven by colonoscopy, and the uptake of fecal tests and sigmoidoscopy gradually declined in the past two decades. Interpretation Despite ongoing progress in CRC screening offers and utilization, there remains large potential for enhanced roll-out and utilization of effective CRC screening programs for enhanced control of CRC incidence and mortality in the years ahead. Funding There was no funding source for this study.


Introduction
Colorectal cancer (CRC) persists as a disease of paramount global health significance, constituting over onetenth of the global cancer burden and leading to approximately one million cancer-related fatalities each year. 1 Nevertheless, the slow development and the long latent phase of the disease and the availability of efficient screening methods provide great opportunities to lower the burden of CRC by population-based CRC screening. 24][5][6] However, these screening tests have either been unavailable or insufficiently utilized in many countries around the world. 7,8[10][11]

Study selection
All citations were imported into Rayyan QCRI systematic review software. 16Titles, abstracts, and full-texts of articles were independently screened by two reviewers (IO, RC) according to eligibility criteria per protocol.The preferred reporting items for systematic reviews and

Research in context
Evidence before this study Despite ample evidence demonstrating the efficacy of diverse colorectal cancer (CRC) screening strategies in reducing CRC incidence and mortality, substantial disparities persist, encompassing the adoption of screening tests by the population, the initiation and types of population screening programs, test availability, and ultimately, utilization rates worldwide.In addition to manually searching the reference lists of relevant published articles, comprehensive literature searches were conducted in PubMed, Web of Science, and Embase from inception to June 2024.Search terms including 'colorectal cancer, or neoplasms, or carcinoma,' were combined with terms such as 'fecal tests,' 'fecal occult blood test,' 'fecal immunochemical test,' 'colonoscopy,' 'endoscopy,' and 'sigmoidoscopy,' as well as terms denoting screening strategies such as 'mass screening,' 'early detection of cancer,' 'population-based screening,' or 'community-based screening.'Our literature search showed that while many countries still fall short of achieving their screening utilization targets, the ongoing evolution and growing adoption of CRC screening guidelines underscore the need for timely documentation of the impact of screening policies and practice decisions over time.In this systematic review, we examined the lifetime and up-to-date utilization of CRC screening tests globally and investigated usage trends over time.

Added value of this study
Our review provides comprehensive documentation and analysis of CRC screening test utilization rates spanning the last four decades.It highlights the impacts and significance of screening test availability, preventive health policies, and the diverse screening guidelines and methodologies implemented across various countries and regions on screening test utilization among eligible populations across the world.

Implications of all the available evidence
In light of the recent development of new guidelines, such as those set forth by the American College of Gastroenterology, alongside ongoing evaluations of existing screening programs, such as the European programs, and the growing adoption of population-based CRC screening beyond Europe and North America, our review offers timely insights with practical and policy implications.These insights have the potential to influence the future trajectory of CRC screening programs, aiming to meet the increasing need to reduce CRC incidence and mortality.meta-analyses (PRISMA) guidelines for reporting of systematic reviews were followed.
Relevant studies that presented national estimates of CRC screening test utilization in the eligible population aged 45 years and older were included in the review.Studies that focused primarily on CRC screening among higher-risk populations, such as those with a family history of CRC, Lynch syndrome, and inflammatory bowel disorders, were excluded.Studies that reported CRC screening use as a follow-up procedure after positive screenings only or CRC treatment were not considered as were those with small sample sizes fewer than 150. 7The data extraction flow chart is presented in Fig. 1, and the list of excluded articles, with reasons and references, is presented in Supplementary appendix 2, Table E1 and Item E2.

Data extraction and quality assessment
Two reviewers (IO and RC) independently and manually extracted data from the included studies using a pretested form in Microsoft® Excel.Information extracted included study characteristics: demographic information of study participants; outcomes studied; and the utilization rate of CRC screening tests.
Quality assessment and risk of bias were independently assessed by two reviewers (IO and RC) using the Effective Public Health Practice Project (EPHPP) assessment tool for observational studies. 17Discrepancies were resolved by discussion between the two reviewers and, where necessary, additional co-authors (HB and MH) to resolve disagreements.

Outcomes
The outcome of interest was the national estimates of utilization of CRC screening tests according to relevant guidelines.Broadly, this involves utilization of guaiacbased fecal occult blood test (gFOBT) or FIT within the last 1-2 years, mt-sDNA within the past 3 years, flexible sigmoidoscopy and CT colonography within the last 5 years, and colonoscopy or endoscopy within the last 5-10 years.

Data synthesis and analysis
Study outcomes were descriptively summarized and results presented by type of CRC screening tests.Unless otherwise specified, weighted proportions were used as reported in studies that used large population-based samples with complex sampling strategy.When reported, the corresponding confidence intervals, as well as age-and sex-specific estimates, were also presented.Due to the disproportionately large number of eligible studies from the US, analysis by type of CRC tests was sub-grouped by location, mainly the US and all other countries.A time trend analysis for utilization of each test was descriptively conducted using studies with consistent outcome definitions.For many countries, we were unable to look at temporal trends in screening utilization because data for several time points was lacking.

Statistics
No statistical tests were applied in the study.

Ethics statement
Patient consent for publication: Not applicable.

Role of the funding source
There was no funding source for this study.

Data sources and quality ratings
From an initial pool of 9165 articles retrieved and screened based on title and abstract, 210 underwent full-text screening.Ultimately, 50 observational studies, offering nationally-representative estimates, were included in the final review spanning data from 1987 to 2021 (Fig. 1).For each EPHPP domain, the quality ratings for the included studies were between low and moderate, essentially due to the self-reported nature of the data (Supplementary appendix 1, Table S2).

Fecal test use in other countries
All studies included from other countries provided estimates for fecal test utilization, except for two studies from Germany 53,54 and one each from Canada 58 and Korea. 50The reported estimates were for fecal tests conducted within 1-2 years, except for studies presenting data on lifetime use (Table 4).
Recent fecal test utilization varied widely among countries.Data from Switzerland between 2007 and 2017 revealed a declining pattern (from 13% to 5.3%) 60,61 similar to the pattern observed in the US.Conversely, findings from the Korean National Cancer Screening Survey indicated a rise in recent fecal test utilization, increasing from 3.8% in 2004 to 27.6% in 2013. 476][57] In Singapore, as of 2008, about one-fifth of the eligible population had recently utilized fecal tests. 62By 2012-2013, utilization had increased to cover close to one-third of the eligible population in both Canada and Korea. 47,49,57 S3).d Sample sizes for the subgroups are very small and may impact the reliability of the subgroup estimates.S6).
Five studies, one each from Singapore, 62 Canada, 57 Korea, 49 Switzerland, 61 and Spain, 65 presented recent utilization estimates by sex, revealing fairly equal utilization between males and females.Additionally, two studies from Canada 56,57 and one each from Korea 49 and Spain 65 S6).

Endoscopy use in other countries
Nineteen studies reporting estimates on the utilization of colonoscopy or sigmoidoscopy were included These  S4).

Description of temporal trends in CRC screening test use
Using data from included studies from 1987, 18-20,22,24- 26,28,29,32,33,35,40,41,43 we observed a steady rise in use of any CRC screening test from approximately 24% in 1987 to 70% in 2020 in the US This increase was predominantly driven by a steep increase in colonoscopy utilization, from nearly 20% in 2000 to 64.5% in 2020. 29,35In contrast, following an initial rise up to 1998, both fecal tests and sigmoidoscopy utilization continuously declined from approximately 20% (fecal tests) and 13.6% (sigmoidoscopy) in 1998 to as low as 7.1% and less than 1%, respectively, in 2015. 19,20,32However, there has been a slight increase in the utilization of these tests since 2016, along with the newly-introduced mt-sDNA (5.8% in 2020) 35 (Fig. 2). Despite slight downturns in 2009-2011 and 2016-2017, the use of any screening tests consistently increased in Korea, driven almost equally by both fecal tests and colonoscopy, mirroring the pattern observed in Canada Conversely, in Switzerland, the prevalence of CRC screening is predominantly propelled by colonoscopy, while the use of fecal tests steadily declined (Figs. 3-6).S6). The pward trend observed in the US was driven by the rapid rise in colonoscopy utilization since the early 2000s.4,11,22 However, recent studies indicate a new surge in the adoption of gFOBT/FIT in the US, as well as the increasing use of mt-sDNA.32,33,66 The surge in colonoscopy utilization is likely strongly linked to its recommendation by US physicians.67 Indeed, despite the challenges associated with colonoscopy, including its high cost, need for rigorous bowel preparation, and potential complications due to its invasive nature, 4 a significant proportion of US primary care physicians reported a considerable uptick in recommending colonoscopy compared to fecal tests, while the volume of recommended sigmoidoscopies decreased substantially.67 This can be partly attributed to the perception of colonoscopy as the gold standard.However, it is also viewed as more readily available, and concerns about potential legal repercussions if not offered to patients have contributed to the significant increase in its recommendation.67 Although colonoscopy has made a significant contribution to accelerating population CRC screening use in the US, there is concern about its potential to exacerbate disparities in healthcare access.As colonoscopy continues to be the predominant screening method, disparities in CRC screening uptake persist along ethnic and racial lines, socioeconomic status, and among the uninsured and underinsured populations.27,35,42,68,69 Except for mt-sDNA, which is only approved in the US, fecal tests have gained widespread adoption in various parts of the world as the primary screening method, with colonoscopy primarily reserved for followup tests following a positive fecal test.4 In Europe, the EU Commission's Independent Expert Report on Cancer Screening recommended FIT as the triage test in organized CRC screening programs.70 While recognizing the superior performance of endoscopic screenings, FIT was considered more acceptable, cost-effective,  S7).

Discussion
Table 5: Estimates of recent and lifetime use of lower GI endoscopy (Colonoscopy or FS) in other countries.a and required less highly skilled manpower. 70These factors contributed to the growing utilization of fecal tests beyond the US.They are equally relevant to resource-constrained regions in Asia, South America, and sub-Saharan Africa, offering an opportunity to enhance screening uptake and alleviate technical and logistical barriers to screening.In the US, the cumulative impact of physicians' favorable attitudes towards colonoscopy, 67 and its unique advantages as the sole single-step test encompassing screening, diagnostic,   S8).  and therapeutic capabilities, 13 might have played a role in its prioritization over fecal tests.Similarly, in contrast to organized screening systems where a two-step approach involving fecal tests could prove effective, the predominantly opportunistic nature of CRC screening in the US makes fecal tests less favorable as a first-line method.This, in part, has influenced the country's CRC screening guidelines. 14ollowing the US Centers for Medicare and Medicaid Services policy that necessitated co-payment for followup colonoscopy after a positive fecal test, in contrast to direct screening colonoscopy, the incentive for fecal test utilization was effectively diminished. 71rious factors may account for the gradual decline in the utilization of FS for CRC screening.The requirement for a follow-up colonoscopy when polyps are detected during screening FS renders it relatively cost-inefficient. 4dditionally, its long-term efficacy in reducing CRC incidence and mortality among women is uncertain. 72onsidering the affordability and procedural simplicity of gFOBT/FIT compared to FS, this might also affect adherence to FS among eligible populations.hile there was notable variability in sex-specific screening utilization over time, the overall age-specific pattern consistently revealed low utilization among younger age groups across all countries and screening methods.Given the anticipated increase in CRC incidence and mortality in the coming decades, 73 the absence of targeted strategies to promote screening uptake among younger, eligible age groups within many existing screening guidelines and programs could exacerbate this detrimental trend.
In the studies reviewed, we observed that a majority of the existing data and population surveys inadequately distinguish between screening and diagnostic tests for CRC.There has been an argument suggesting that differentiating between screening and non-screening CRC tests is inconsequential, as repeat screening tests are deemed unnecessary even when initially conducted for non-screening purposes. 33,57Nonetheless, segregating the tests facilitates a precise assessment of screening program effectiveness, preventive health  education, and the identification and potential resolution of barriers and disparities in access and utilization of these tests. 20espite the proven reliability of self-reported surveys, 74 achieving complete discrimination between screening and non-screening tests remains challenging. 75However, incorporating comprehensive supporting information in the surveys and encouraging interviewers, where applicable, to diligently explain the distinctions can be beneficial.Additionally, the creation of distinct questions for screening and non-screening CRC tests in surveys may prompt respondents to think critically about the accuracy of the information they provide.
Due to the paucity of studies 7 and our emphasis on nationally representative reports, this review did not include estimates from countries in Africa, South America, and much of Asia.This may potentially reflect the limited availability of CRC screening tests, the absence of population-based screening programs, or the lack of research-centric population health surveys and databases in these regions.Nevertheless, the costeffectiveness of screening colonoscopy and FIT has been established in some parts of Asia and Africa, 76,77 and feasibility studies have been suggested to explore the implementation of FIT-based screening in Africa. 78 recent review identified a lack of infrastructure and trained personnel for endoscopy, along with insufficient patient education about CRC screening, as barriers to screening in Africa.78 Addressing these potential barriers is crucial, and there is a need to integrate proven screening strategies tailored to local resources and technical and logistical peculiarities.
In a large population like China, most CRC screening programs are predominantly conducted at provincial and municipal levels, with two central and four regional-level programs initiated as of 2020. 79owever, most research has focused on evaluating program-specific metrics rather than the overall population-level screening utilization rates.A recent review showed that the national average screening coverage among the eligible age group (40-74 years) across these existing programs-including organized, opportunistic, and physical examination pathways-remains approximately 3%. 79rogressively, as many countries strive to achieve diverse population CRC screening utilization targets, the emphasis should be on enhancing accessibility, affordability, eliminating disparities in access, and adopting resource-effective strategies.The implementation of organized CRC screening programs has proven effective in enhancing screening uptake, for example in Europe, particularly when implemented on a national scale. 8,10lso, the implementation of organized screening guidelines with FIT could empower physicians in their messaging and recommendations.It has been demonstrated to rapidly increase CRC screening utilization, particularly in regions previously operating opportunistic programs. 80The recent American College of Gastroenterology guidelines recommending a FITbased organized system could further accelerate CRC screening utilization. 14Moreover, the concurrent implementation of the new US Centers for Medicare and Medicaid Services cost coverage for follow-on colonoscopy may offer synergistic support, contributing to the reduction of disparities in CRC screening. 71urthermore, the availability of multiple screening alternatives could attract individuals with diverse screening preferences. 14Combining various strategies to mobilize eligible individuals is likely to enhance test utilization, even within organized screening systems. 14,81 key strength of this study is its inclusion of studies exclusively utilizing nationally representative data.The analysis of time trends in CRC screening test utilization, especially in the US, offers a comprehensive overview of the progress achieved over the past three decades, providing an opportunity to understand how various policies and guidelines have impacted screening utilization.
A limitation of the study is that majority of eligible studies were identified in the US, largely owing to the consistent availability of population-based data like NHIS over several decades.In contrast, eligible studies from other regions are limited or sometimes absent, making it challenging to form a comprehensive understanding of screening utilization over the long term.Similarly, we cannot rule out potential biases that might have been introduced due to non-inclusion of studies which utilized regional/provincial-level data or data from large population subgroups.
Additionally, since the included studies predominantly relied on self-reported data, the risk of recall and reporting biases, with the potential for both overestimation and underestimation of screening test use, cannot be ruled out.
Overall, CRC screening tests remain underutilized in many countries, notwithstanding the rising colonoscopy-driven trends in the US and the increasing adoption of triage fecal tests in Europe and a few other countries.Efforts to reduce CRC incidence and mortality rely on wide coverage and utilization of proven screening tests by all eligible individuals.Hence, without discarding other screening options, including sigmoidoscopy, the implementation of organized, FITbased programs could be a cost-efficient strategy to rapidly increase screening uptake, even in resourcelimited settings.
Distinguishing between screening and nonscreening tests in surveys is useful.Where resources permit, regular population-based surveys are encouraged to facilitate prompt, policy-relevant decision-making for addressing screening uptake and various barriers to screening utilization.

Fig. 1 :
Fig. 1: Flowchart of the article selection process for the review.
Abbreviations: CCHS, Canadian Community Health Survey; HH survey, Household survey; KNCSS, Korean National Cancer Screening Survey; SHIS, Swiss Health Interview Survey; SNSEH, Saudi National Survey for Elderly Health; EHIS, European Health Interview Survey; FOBT, fecal occult blood test; FIT, fecal immunochemical test; Endo, endoscopy; Col., colonoscopy; FS, flexible sigmoidoscopy; DCBE, double-contrast barium enema; NR, not reported; yr(s), year(s).a Table ordered first according to country (in alphabetical order), then the year of data collection.b Data calculated from the available information in the article.c Up-to-date with CRC screening was defined as FIT within 1 year, or DCBE within 5 years, or colonoscopy within 10 years in 2005-2018.This was changed to FIT within 1 year or colonoscopy within 10 years in 2019-2020.50d  Other information (e.g.estimates for other years reported in the study, or estimates by age or sex) are provided in TableS8).

Fig. 2 :
Fig. 2: Trends in CRC screening utilization in the US, 1987-2020.Circle size represents relative sample size.Only studies that used test intervals consistent with national guidelines were included in the examination of trends; i.e fecal occult blood test/fecal immunochemical test (FOBT/FIT) within 1 year, colonoscopy within 10 years, sigmoidoscopy or computed tomographic (CT) colonography within 5 years, or multitarget stool DNA (mt-sDNA) within 3 years.

Fig. 3 :
Fig. 3: Trends in CRC screening utilization in other countries (Canada, Switzerland, and Korea, 2003-2020).Countries with estimates for at least three time points and with test intervals consistent with respective national guidelines were included in the examination of trends.Circle size represents relative sample size.FIT, fecal immunochemical test.Until 2009, up-to-date screening in Korea involved the utilization of either colonoscopy within 5 years, double-contrast barium enema (DCBE) within 5 years, or fecal occult blood test (FOBT) within a year.Subsequently, the interval for colonoscopy was extended to 10 years, and DCBE was excluded from the recommendations starting in 2018.47,54

Table 1 :
Estimates 8,10ecent and lifetime use of fecal test (gFOBT or FIT, or mt-sDNA) from the United States.aCardosoetal.8andOlaetal.10providedestimatescategorized by type of CRC screening offer.Utilization within the past two years ranged from 3.6% in Romania to 51.5% in France in 2013-20158and from 3.6% in Bulgaria to 67.1% in Denmark in 2018-2020, 10 with more favorable rates overall observed in countries offering fecal tests within fully implemented national organized screening programs8,10(Table reported recent fecal test use by age group.Utilization generally increased with increasing age, and was highest in age group 64-74 years (Table

Table 3 :
Estimates of use of fecal tests, FS and/or colonoscopy (combined) in the United States.
a Combined use of fecal tests, flexible sigmoidoscopy and/or colonoscopy in other countries This review summarizes national estimates of CRC screening test utilization among eligible age groups Abbreviations: CCHS, Canadian Community Health Survey; HH survey, Household survey; HCAP, Health Care Access Panel; KNCSS, Korean National Cancer Screening Survey; SHIS, Swiss Health Interview Survey; SNSEH, Saudi National Survey for Elderly Health; EHIS, European Health Interview Survey; AHIS, Austrian Health Interview Survey; SNHS, Spanish National Health Survey; EHS, European Health Survey; GHU, German Health Update; gFOBT, guaiac-based fecal occult blood test; NR, not reported; yr(s), year(s).a Table ordered first according to country (in alphabetical order), then the year of data collection.b Data calculated from the available information in the article.c Other information (e.g.estimates for other years reported in the study, or estimates by age or sex) are provided in Table

Table 4 :
Estimates of recent and lifetime use of fecal test (gFOBT or FIT) in other countries.a

Table 6 :
Estimates of use of any CRC Screening test in other countries.a